The pathogen Staphylococcus aureus uses various strategies for persisting in the host, among which switching to a small-colony variant (SCV) phenotype is of particular biological and therapeutic significance. Phenotypically, SCVs are characterized by a slow growth rate, atypical colony morphology and unusual biochemical features, constituting a real challenge for identification by the clinical microbiology laboratory. Their metabolic defects also alter their susceptibility to antibiotics, which, combined with the ability to survive intracellularly and, for some strains, to form biofilms, largely contributes to therapeutic failures. This paper reviews the available literature on antibiotic activity against SCVs of S. aureus in vitro, in animal models and in clinics. In vitro, aminoglycosides and antifolate agents show high MICs for electron-transport-defective and thymidine-dependent SCVs, respectively. The other antibiotic classes usually show MICs comparable to those measured for the parental strains, but they are less bactericidal. Intracellularly, auxotrophs for thymidine, haemin or menadione show contrasting behaviours with respect to their response to antibiotics, resulting from differences in their intracellular fate. In animal models, SCVs often persist in various locations, including metastatic ones, in spite of the administration of active antibiotics. In healthcare, several case reports mention the selection of SCVs after prolonged administration of not only aminoglycosides and antifolate agents, but also several other antibiotic classes. Apparent eradication requires several weeks or even months of aggressive polytherapy combined, whenever possible, with surgical intervention. Further research is thus warranted for optimizing the treatment of infections caused by SCVs.

Staphylococcus aureus produces a particular morphological variant called small colony variant (SCV) which is responsible for persistent subclinical infections in predisposed individuals and is usually resistant to aminoglycosides and cell wall active antibiotics. Infections by SCV of S. aureus are an upcoming problem due to difficulty in laboratory diagnosis and resistance to antimicrobial chemotherapy. We here report a case of infective endocarditis caused by SCV of Staphylococcus aureus in a pediatric patient.